{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T21:06:56Z","timestamp":1791234416602,"version":"4.1.0"},"reference-count":67,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2020,5,12]],"date-time":"2020-05-12T00:00:00Z","timestamp":1589241600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100009045","name":"Uniwersytet Jagiello\u0144ski Collegium Medicum","doi-asserted-by":"publisher","award":["N41\/DBS\/000105"],"award-info":[{"award-number":["N41\/DBS\/000105"]}],"id":[{"id":"10.13039\/100009045","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004281","name":"Narodowe Centrum Nauki","doi-asserted-by":"publisher","award":["UMO-2019\/33\/B\/NZ4\/00616"],"award-info":[{"award-number":["UMO-2019\/33\/B\/NZ4\/00616"]}],"id":[{"id":"10.13039\/501100004281","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004281","name":"Narodowe Centrum Nauki","doi-asserted-by":"publisher","award":["UMO-2016\/23\/N\/NZ4\/01890"],"award-info":[{"award-number":["UMO-2016\/23\/N\/NZ4\/01890"]}],"id":[{"id":"10.13039\/501100004281","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Exposure to acidic gastric content due to malfunction of lower esophageal sphincter leads to acute reflux esophagitis (RE) leading to disruption of esophageal epithelial cells. Carbon monoxide (CO) produced by heme oxygenase (HMOX) activity or released from its donor, tricarbonyldichlororuthenium (II) dimer (CORM-2) was reported to protect gastric mucosa against acid-dependent non-steroidal anti-inflammatory drug-induced damage. Thus, we aimed to investigate if CO affects RE-induced esophageal epithelium lesions development. RE induced in Wistar rats by the ligation of a junction between pylorus and forestomach were pretreated i.g. with vehicle CORM-2; RuCl3; zinc protoporphyrin IX, or hemin. CORM-2 was combined with NG-nitro-L-arginine (L-NNA), indomethacin, capsazepine, or capsaicin-induced sensory nerve ablation. Esophageal lesion score (ELS), esophageal blood flow (EBF), and mucus production were determined by planimetry, laser flowmetry, histology. Esophageal Nrf-2, HMOXs, COXs, NOSs, TNF-\u03b1 and its receptor, IL-1 family and IL-1 receptor antagonist (RA), NF-\u03baB, HIF-1\u03b1, annexin-A1, suppressor of cytokine signaling (SOCS3), TRPV1, c-Jun, c-Fos mRNA\/protein expressions, PGE2, 8-hydroxy-deoxyguanozine (8-OHdG) and serum COHb, TGF-\u03b21, TGF-\u03b22, IL-1\u03b2, and IL-6 content were assessed by PCR, immunoblotting, immunohistochemistry, gas chromatography, ELISA or Luminex platform. Hemin or CORM-2 alone or combined with L-NNA or indomethacin decreased ELS. Capsazepine or capsaicin-induced denervation reversed CORM-2 effects. COHb blood content, esophageal HMOX-1, Nrf-2, TRPV1 protein, annexin-A1, HIF-1\u03b1, IL-1 family, NF-\u03baB, c-Jun, c-Fos, SOCS3 mRNA expressions, and 8-OHdG levels were elevated while PGE2 concentration was decreased after RE. CO donor-maintained elevated mucosal TRPV1 protein, HIF-1 \u03b1, annexin-A1, IL-1RA, SOCS3 mRNA expression, or TGF-\u03b2 serum content, decreasing 8-OHdG level, and particular inflammatory markers expression\/concentration. CORM-2 and Nrf-2\/HMOX-1\/CO pathway prevent esophageal mucosa against RE-induced lesions, DNA oxidation, and inflammatory response involving HIF-1\u03b1, annexin-A1, SOCS3, IL-1RA, TGF-\u03b2-modulated pathways. Esophagoprotective and hyperemic CO effects are in part mediated by afferent sensory neurons and TRPV1 receptors activity with questionable COX\/PGE2 or NO\/NOS systems involvement.<\/jats:p>","DOI":"10.3390\/cells9051203","type":"journal-article","created":{"date-parts":[[2020,5,12]],"date-time":"2020-05-12T10:53:55Z","timestamp":1589280835000},"page":"1203","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Evidence for Cytoprotective Effect of Carbon Monoxide Donor in the Development of Acute Esophagitis Leading to Acute Esophageal Epithelium Lesions"],"prefix":"10.3390","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4866-1102","authenticated-orcid":false,"given":"Katarzyna","family":"Magierowska","sequence":"first","affiliation":[{"name":"Department of Physiology, Jagiellonian University Medical College, 31-531 Cracow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominik","family":"Bakalarz","sequence":"additional","affiliation":[{"name":"Department of Physiology, Jagiellonian University Medical College, 31-531 Cracow, Poland"},{"name":"Department of Forensic Toxicology, Institute of Forensic Research, 31-033 Cracow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3098-9617","authenticated-orcid":false,"given":"Dagmara","family":"W\u00f3jcik","sequence":"additional","affiliation":[{"name":"Department of Physiology, Jagiellonian University Medical College, 31-531 Cracow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edyta","family":"Korbut","sequence":"additional","affiliation":[{"name":"Department of Physiology, Jagiellonian University Medical College, 31-531 Cracow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aleksandra","family":"Danielak","sequence":"additional","affiliation":[{"name":"Department of Physiology, Jagiellonian University Medical College, 31-531 Cracow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Urszula","family":"G\u0142owacka","sequence":"additional","affiliation":[{"name":"Department of Physiology, Jagiellonian University Medical College, 31-531 Cracow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Pajdo","sequence":"additional","affiliation":[{"name":"Department of Physiology, Jagiellonian University Medical College, 31-531 Cracow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7637-6387","authenticated-orcid":false,"given":"Grzegorz","family":"Buszewicz","sequence":"additional","affiliation":[{"name":"Department of Forensic Medicine, Medical University of Lublin, 20-090 Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6700-2906","authenticated-orcid":false,"given":"Grzegorz","family":"Ginter","sequence":"additional","affiliation":[{"name":"Department of Physiology, Jagiellonian University Medical College, 31-531 Cracow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcin","family":"Surmiak","sequence":"additional","affiliation":[{"name":"Department of Physiology, Jagiellonian University Medical College, 31-531 Cracow, Poland"},{"name":"Department of Internal Medicine, Jagiellonian University Medical College, 31-066 Cracow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4806-8042","authenticated-orcid":false,"given":"S\u0142awomir","family":"Kwiecie\u0144","sequence":"additional","affiliation":[{"name":"Department of Physiology, Jagiellonian University Medical College, 31-531 Cracow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Chmura","sequence":"additional","affiliation":[{"name":"Department of Physiology, Jagiellonian University Medical College, 31-531 Cracow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0175-5600","authenticated-orcid":false,"given":"Marcin","family":"Magierowski","sequence":"additional","affiliation":[{"name":"Department of Physiology, Jagiellonian University Medical College, 31-531 Cracow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5805-0065","authenticated-orcid":false,"given":"Tomasz","family":"Brzozowski","sequence":"additional","affiliation":[{"name":"Department of Physiology, Jagiellonian University Medical College, 31-531 Cracow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,5,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1007\/s10620-014-3349-2","article-title":"Aspirin and nonsteroidal anti-inflammatory drug use and the risk of Barrett\u2019s esophagus","volume":"60","author":"Schneider","year":"2015","journal-title":"Dig. 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